Age and Sex Impact Clozapine Plasma Concentrations in Inpatients and Outpatients With Schizophrenia

摘要: Background Although clozapine is primarily used in a younger to mid-life population of patients with psychosis, there are limited data on the clinical pharmacology later life. The objective this study was assess magnitude and variability plasma concentrations norclozapine across lifespan real-world setting. Design A pharmacokinetic using nonlinear mixed effect modeling (NONMEM). Age, sex, height, weight, dosage formulation were covariates. Setting Inpatients outpatients at Centre for Addiction Mental Health, Toronto, from 2001 2007. Participants Patients ranging ages 11 79 schizophrenia spectrum disorders prescribed (Clozaril). Measurements total 1142 (2,284 concentration measurements) 391 disorder. Results one-compartment model first-order absorption elimination best described data. predicted clearance females 27.1 L/h (SE 11.1%) 36.7 9.7%) males. For norclozapine, 48.6 10.8%) 63.1 9.3%) only covariates significant age sex: both parent metabolite decreased exponentially least 39 years. Conclusions Decreased results increased blood and, hence, potential adverse drug reactions. These findings have particular relevance dosing safety monitoring older adults, highlighting need vigilance.